Xiaoling Yin, Juan Meng, Stephen R. Durham, Stefano Del Giacco, Lisha Li, Hae‐Sim Park, Maria Jose Torres, Philip H. Li, Mohamed Shamji
{"title":"East Meets West in Allergic Airway Disease: Insights From the EAACI Hong Kong Allergy School 2025","authors":"Xiaoling Yin, Juan Meng, Stephen R. Durham, Stefano Del Giacco, Lisha Li, Hae‐Sim Park, Maria Jose Torres, Philip H. Li, Mohamed Shamji","doi":"10.1111/all.70204","DOIUrl":"https://doi.org/10.1111/all.70204","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"22 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya‐Qi Peng, Te Zhang, Xiao‐Qing Liu, Ismail Ogulur, Qi Sun, Beate Ruckert, Bi‐Xin He, De‐Hua Chen, Hideaki Morita, Hui‐Jing Ye, Qing‐Ling Fu, Cezmi A. Akdis
Background Innate lymphoid cells (ILCs) are classically divided into three groups: ILC1, ILC2, and ILC3 to reflect their functional analogy to Th1, Th2, and Th17. There is also an IL‐9 single‐producing T cell subset, namely the Th9 cell, which plays a dominant role in the onset of allergic diseases compared with traditional Th2 cells. Although a corresponding cell subset of ILCs to different Th cell subsets exists, so far the counterpart of Th9 cells in ILCs has not been reported. Objective In this study, we aimed to report the existence of group 9 innate lymphoid cells (ILC9s) and characterize them in allergic rhinitis (AR) and in response to allergen immunotherapy. Methods The expressions and characterization of ILC9s were investigated in purified ILCs cultures, PBMCs from patients with AR and responder subcutaneous immunotherapy (SCIT) patients by flow cytometry, scRNA‐seq transcriptome, qRT‐PCR, siRNA knockdown, and immunofluorescence staining. Results IL‐9‐expressing cells were observed in the nasal mucosa of patients with AR without the co‐expression of IL‐5 and IL‐13. IL‐4 and TGF‐β induce IL‐9 secretion by human ILCs. scRNA‐seq of whole ILCs defines an H1R + OX‐40L − ILC subset as ILC9 expressing high levels of IL‐9 and low levels of the ILC2 transcription factor GATA3. Instead, this new ILC9 subset displays Bach2 as a transcription factor, and IL‐9 expression decreases after siRNA inhibition of Bach2. Histamine is an important regulator of ILC9 because ILC9 production increases in response to histamine, and IL‐9 levels in ILCs positively correlate with the expression of histamine 1R. An up‐regulation of PPARγ was observed in ILCs in response to IL‐4 and TGF‐β, and ILC9 differentiation was suppressed by the PPARγ antagonist. Conclusion ILC9s are highly expressed in the nasal mucosa and PBMCs of patients with AR and were decreased in response to house dust mite–SCIT. Our study sheds light on the newly discovered ILC9 subset and demonstrates a potential target in allergen immunotherapy.
{"title":"Characterization of Human Group 9 Innate Lymphoid Cells in Response to Allergen Immunotherapy in Patients With Allergic Rhinitis","authors":"Ya‐Qi Peng, Te Zhang, Xiao‐Qing Liu, Ismail Ogulur, Qi Sun, Beate Ruckert, Bi‐Xin He, De‐Hua Chen, Hideaki Morita, Hui‐Jing Ye, Qing‐Ling Fu, Cezmi A. Akdis","doi":"10.1111/all.70202","DOIUrl":"https://doi.org/10.1111/all.70202","url":null,"abstract":"Background Innate lymphoid cells (ILCs) are classically divided into three groups: ILC1, ILC2, and ILC3 to reflect their functional analogy to Th1, Th2, and Th17. There is also an IL‐9 single‐producing T cell subset, namely the Th9 cell, which plays a dominant role in the onset of allergic diseases compared with traditional Th2 cells. Although a corresponding cell subset of ILCs to different Th cell subsets exists, so far the counterpart of Th9 cells in ILCs has not been reported. Objective In this study, we aimed to report the existence of group 9 innate lymphoid cells (ILC9s) and characterize them in allergic rhinitis (AR) and in response to allergen immunotherapy. Methods The expressions and characterization of ILC9s were investigated in purified ILCs cultures, PBMCs from patients with AR and responder subcutaneous immunotherapy (SCIT) patients by flow cytometry, scRNA‐seq transcriptome, qRT‐PCR, siRNA knockdown, and immunofluorescence staining. Results IL‐9‐expressing cells were observed in the nasal mucosa of patients with AR without the co‐expression of IL‐5 and IL‐13. IL‐4 and TGF‐β induce IL‐9 secretion by human ILCs. scRNA‐seq of whole ILCs defines an H1R <jats:sup>+</jats:sup> OX‐40L <jats:sup>−</jats:sup> ILC subset as ILC9 expressing high levels of IL‐9 and low levels of the ILC2 transcription factor GATA3. Instead, this new ILC9 subset displays Bach2 as a transcription factor, and IL‐9 expression decreases after siRNA inhibition of Bach2. Histamine is an important regulator of ILC9 because ILC9 production increases in response to histamine, and IL‐9 levels in ILCs positively correlate with the expression of histamine 1R. An up‐regulation of PPARγ was observed in ILCs in response to IL‐4 and TGF‐β, and ILC9 differentiation was suppressed by the PPARγ antagonist. Conclusion ILC9s are highly expressed in the nasal mucosa and PBMCs of patients with AR and were decreased in response to house dust mite–SCIT. Our study sheds light on the newly discovered ILC9 subset and demonstrates a potential target in allergen immunotherapy.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"25 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alain Didier, Ruta Gronskyte Juhl, Terrie Dalgaard, Antoine Chartier, Philippe Devillier
Background Tablet formulations of allergen extracts are widely recommended over other formulations for the sublingual immunotherapy (SLIT) of respiratory allergies. However, with adequate clinical trial evidence, SLIT (liquid) drop formulations may be a relevant allergy treatment option. Methods The RHAPSODY multinational, Phase III, parallel‐group, double‐blind, placebo‐controlled, randomised clinical study of adults with moderate‐to‐severe, grass‐pollen‐induced allergic rhinoconjunctivitis (ARC) with or without asthma was conducted at 45 investigating centres in six European countries. Participants received 26 months of continuous treatment with active 5‐grass‐pollen SLIT drops or placebo. The primary efficacy endpoint was the average daily total combined score (TCS, comprising a symptom score and a rescue medication score) during the second peak grass pollen season (PGPS). Results Of the 445 randomised patients (mean ± standard deviation (range) age: 32.6 ± 9.9 (18–63); males: 55.1%), 389 completed the trial. The primary efficacy endpoint showed a statistically significant difference in favour of active treatment versus placebo (average difference in the daily TCS: 1.88 (95% CI: 0.60–3.17); relative difference 26.51% (95% CI: 9.42–40.55); p = 0.0036). The difference (0.17 points) in the average weekly Rhinitis Quality of Life Questionnaire score during the second PGPS in favour of the active treatment was clinically relevant but not statistically significant. The differences in efficacy were generally driven by the medication score, rather than the symptom score. Most adverse events were mild and local. Conclusions RHAPSODY was the first well‐powered clinical trial to show the positive risk–benefit ratio of 5‐grass‐pollen SLIT drops in adult participants with moderate‐to‐severe grass‐pollen‐induced ARC.
{"title":"Five‐Grass‐Pollen Sublingual Immunotherapy Drops Are Efficacious and Well Tolerated in Adults: The RHAPSODY Phase III Trial","authors":"Alain Didier, Ruta Gronskyte Juhl, Terrie Dalgaard, Antoine Chartier, Philippe Devillier","doi":"10.1111/all.70191","DOIUrl":"https://doi.org/10.1111/all.70191","url":null,"abstract":"Background Tablet formulations of allergen extracts are widely recommended over other formulations for the sublingual immunotherapy (SLIT) of respiratory allergies. However, with adequate clinical trial evidence, SLIT (liquid) drop formulations may be a relevant allergy treatment option. Methods The RHAPSODY multinational, Phase III, parallel‐group, double‐blind, placebo‐controlled, randomised clinical study of adults with moderate‐to‐severe, grass‐pollen‐induced allergic rhinoconjunctivitis (ARC) with or without asthma was conducted at 45 investigating centres in six European countries. Participants received 26 months of continuous treatment with active 5‐grass‐pollen SLIT drops or placebo. The primary efficacy endpoint was the average daily total combined score (TCS, comprising a symptom score and a rescue medication score) during the second peak grass pollen season (PGPS). Results Of the 445 randomised patients (mean ± standard deviation (range) age: 32.6 ± 9.9 (18–63); males: 55.1%), 389 completed the trial. The primary efficacy endpoint showed a statistically significant difference in favour of active treatment versus placebo (average difference in the daily TCS: 1.88 (95% CI: 0.60–3.17); relative difference 26.51% (95% CI: 9.42–40.55); <jats:italic>p</jats:italic> = 0.0036). The difference (0.17 points) in the average weekly Rhinitis Quality of Life Questionnaire score during the second PGPS in favour of the active treatment was clinically relevant but not statistically significant. The differences in efficacy were generally driven by the medication score, rather than the symptom score. Most adverse events were mild and local. Conclusions RHAPSODY was the first well‐powered clinical trial to show the positive risk–benefit ratio of 5‐grass‐pollen SLIT drops in adult participants with moderate‐to‐severe grass‐pollen‐induced ARC.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"73 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. A. Nagy, D. Schnoegl, V. Houghton, L. O'Mahony, A. F. Santos, E. F. Knol, A. Kuehn, T. Eiwegger
Food allergies (FA) represent a significant global health burden. Upon allergen re‐exposure, allergic patients exhibit a sequence of symptoms that vary in terms of affected organ systems, severity, time of onset and allergen reactivity thresholds. This review focuses on the sequence of immediate immunological and clinical events that occur during allergen exposure in individuals with FA. It highlights both clinical and immunological baseline risk factors and discusses recent advances in understanding the acute allergic response. We explore the implications of immune mechanistic knowledge for predicting clinical reactivity and therapy of FA. The current diagnostic gold standard, the oral food challenge (OFC), may help identify early biomarkers for patient stratification and provide insights into the immune dynamics underlying acute allergic reactions in vivo.
{"title":"Sequence of Immunological Events During IgE ‐Mediated Allergic Reactions to Food","authors":"N. A. Nagy, D. Schnoegl, V. Houghton, L. O'Mahony, A. F. Santos, E. F. Knol, A. Kuehn, T. Eiwegger","doi":"10.1111/all.70194","DOIUrl":"https://doi.org/10.1111/all.70194","url":null,"abstract":"Food allergies (FA) represent a significant global health burden. Upon allergen re‐exposure, allergic patients exhibit a sequence of symptoms that vary in terms of affected organ systems, severity, time of onset and allergen reactivity thresholds. This review focuses on the sequence of immediate immunological and clinical events that occur during allergen exposure in individuals with FA. It highlights both clinical and immunological baseline risk factors and discusses recent advances in understanding the acute allergic response. We explore the implications of immune mechanistic knowledge for predicting clinical reactivity and therapy of FA. The current diagnostic gold standard, the oral food challenge (OFC), may help identify early biomarkers for patient stratification and provide insights into the immune dynamics underlying acute allergic reactions in vivo.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"28 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine Moermans, Mare Sabbe, Adrien Onssels, Noémie Bricmont, Romane Bonhiver, France Regnier, Sophie Graff, Sara Gerday, Makon‐Sébastien Njock, Adeline Rosu, Virginie Paulus, Françoise Guissard, Stéphanie Ziant, Carole Sanchez, Marie Ernst, Christophe Desmet, Renaud Louis, Florence Schleich
{"title":"Dupilumab Effectiveness in Biologic‐Naïve and Switched Severe Asthma in Real Life","authors":"Catherine Moermans, Mare Sabbe, Adrien Onssels, Noémie Bricmont, Romane Bonhiver, France Regnier, Sophie Graff, Sara Gerday, Makon‐Sébastien Njock, Adeline Rosu, Virginie Paulus, Françoise Guissard, Stéphanie Ziant, Carole Sanchez, Marie Ernst, Christophe Desmet, Renaud Louis, Florence Schleich","doi":"10.1111/all.70205","DOIUrl":"https://doi.org/10.1111/all.70205","url":null,"abstract":"","PeriodicalId":122,"journal":{"name":"Allergy","volume":"45 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Remo Poto, Rory Chan, Corrado Pelaia, G. Walter Canonica, J. Christian Virchow, Gilda Varricchi
Asthma is a chronic inflammatory respiratory disease, affecting hundreds of millions of individuals worldwide. Mucous hypersecretion, which leads to the formation of mucous plugs within the airways, is a key pathophysiological feature associated with severe asthma and airway remodeling. Persistent airflow obstruction due to mucous plugging has been recognized as a contributor to poor symptom control in patients with asthma. This phenomenon is driven by type 2 inflammation, mediated by elevated levels of IL‐5 and IL‐13, as well as eosinophilic infiltration, which collectively promote the formation and persistence of mucous plugs. The presence of mucous plugging has been linked to the frequency and severity of exacerbations, as well as airflow obstruction. Imaging modalities such as high‐resolution computed tomography (HRCT), hyperpolarized 129 Xe MRI, and optical coherence tomography (OCT) have provided insights into the extent of mucous plugging and its association with airflow limitation. Over the past decade, biological therapies targeting specific pathways of type 2 inflammation have emerged as highly effective treatment options for patients with severe asthma. These therapies have conferred substantial improvements in lung function, reduction in exacerbation rates, and decreased oral glucocorticoid use. One of their mechanisms of action might be due to removal of persistent mucous plugs not achieved by conventional anti‐asthmatic therapies such as inhaled corticosteroids (ICS) and oral corticosteroids (OCS). This comprehensive review summarizes the effects of biologics on mucous plugging in severe asthma, focusing on their mechanisms of action, clinical efficacy, and potential implications for optimizing treatment strategies.
{"title":"The Role of Biologics in Reducing Mucous Plug Burden in Asthma","authors":"Remo Poto, Rory Chan, Corrado Pelaia, G. Walter Canonica, J. Christian Virchow, Gilda Varricchi","doi":"10.1111/all.70197","DOIUrl":"https://doi.org/10.1111/all.70197","url":null,"abstract":"Asthma is a chronic inflammatory respiratory disease, affecting hundreds of millions of individuals worldwide. Mucous hypersecretion, which leads to the formation of mucous plugs within the airways, is a key pathophysiological feature associated with severe asthma and airway remodeling. Persistent airflow obstruction due to mucous plugging has been recognized as a contributor to poor symptom control in patients with asthma. This phenomenon is driven by type 2 inflammation, mediated by elevated levels of IL‐5 and IL‐13, as well as eosinophilic infiltration, which collectively promote the formation and persistence of mucous plugs. The presence of mucous plugging has been linked to the frequency and severity of exacerbations, as well as airflow obstruction. Imaging modalities such as high‐resolution computed tomography (HRCT), hyperpolarized <jats:sup>129</jats:sup> Xe MRI, and optical coherence tomography (OCT) have provided insights into the extent of mucous plugging and its association with airflow limitation. Over the past decade, biological therapies targeting specific pathways of type 2 inflammation have emerged as highly effective treatment options for patients with severe asthma. These therapies have conferred substantial improvements in lung function, reduction in exacerbation rates, and decreased oral glucocorticoid use. One of their mechanisms of action might be due to removal of persistent mucous plugs not achieved by conventional anti‐asthmatic therapies such as inhaled corticosteroids (ICS) and oral corticosteroids (OCS). This comprehensive review summarizes the effects of biologics on mucous plugging in severe asthma, focusing on their mechanisms of action, clinical efficacy, and potential implications for optimizing treatment strategies.","PeriodicalId":122,"journal":{"name":"Allergy","volume":"29 1","pages":""},"PeriodicalIF":12.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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